ADAA_ASPNG
ID ADAA_ASPNG Reviewed; 1793 AA.
AC G3KLH6;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Non-reducing polyketide synthase adaA {ECO:0000303|PubMed:21866960};
DE Short=NRPKS adaA {ECO:0000303|PubMed:21866960};
DE EC=2.3.1.- {ECO:0000269|PubMed:21866960};
DE AltName: Full=2-acetyl-2-decarboxamidoanthrotainin biosynthesis cluster protein A {ECO:0000303|PubMed:21866960};
GN Name=adaA {ECO:0000303|PubMed:21866960}; ORFNames=ATCC64974_92700;
OS Aspergillus niger.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=5061;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, DOMAIN, FUNCTION,
RP CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=ATCC 1015 / NV DSM 2061;
RX PubMed=21866960; DOI=10.1021/ja206906d;
RA Li Y., Chooi Y.H., Sheng Y., Valentine J.S., Tang Y.;
RT "Comparative characterization of fungal anthracenone and naphthacenedione
RT biosynthetic pathways reveals an alpha-hydroxylation-dependent Claisen-like
RT cyclization catalyzed by a dimanganese thioesterase.";
RL J. Am. Chem. Soc. 133:15773-15785(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 64974 / FGSC A733 / N402;
RX PubMed=30319579; DOI=10.3389/fmicb.2018.02269;
RA Laothanachareon T., Tamayo-Ramos J.A., Nijsse B., Schaap P.J.;
RT "Forward genetics by genome sequencing uncovers the central role of the
RT Aspergillus niger goxB locus in hydrogen peroxide induced glucose oxidase
RT expression.";
RL Front. Microbiol. 9:2269-2269(2018).
CC -!- FUNCTION: Non-reducing polyketide synthase (NRPKS); part of the gene
CC cluster that mediates the biosynthesis of the linear tetracyclic TAN-
CC 1612 neuropeptide Y receptor antagonist (PubMed:21866960). The
CC decaketide backbone of TAN-1612 is synthesized by the non-reducing
CC polyketide synthase adaA via condensation of one acetyl-CoA starter
CC unit with 9 malonyl-CoA units. The FAD-dependent monooxygenase adaC
CC then performs hydroxylation at C2 while the polaketide chain is still
CC attached to the NRPKS adaA (PubMed:21866960). The alpha-hydroxylation
CC step at C2 appears to be crucial for the following C18-C1 Claisen
CC cyclization and release of the C9-hydroxyl version of TAN-1612 from the
CC NRPKS adaA, two steps performed by the lactamase-like protein adaB
CC (PubMed:21866960). Finally, the O-methyltransferase adaD performs the
CC C9 O-methylation to complete the biosynthesis of TAN-1612
CC (PubMed:21866960). {ECO:0000269|PubMed:21866960}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 9 H(+) + holo-[ACP] + 9 malonyl-CoA = 3-(2,4-
CC dioxopentyl)-3,6,8,9-tetrahydroxy-1-oxo-1,2,3,4-tetrahydroanthracene-
CC 2-carboxyl-[ACP] + 9 CO2 + 10 CoA + 2 H2O; Xref=Rhea:RHEA:64088,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:16518, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:149687; Evidence={ECO:0000269|PubMed:21866960};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64089;
CC Evidence={ECO:0000269|PubMed:21866960};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:A0A0K0MCJ4};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:21866960}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm. {ECO:0000305|PubMed:21866960}.
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DR EMBL; JN257714; AEN83889.1; -; Genomic_DNA.
DR EMBL; OGUI01000016; SPB51660.1; -; Genomic_DNA.
DR AlphaFoldDB; G3KLH6; -.
DR SMR; G3KLH6; -.
DR STRING; 5061.CADANGAP00008887; -.
DR VEuPathDB; FungiDB:An11g07310; -.
DR VEuPathDB; FungiDB:ASPNIDRAFT2_1112167; -.
DR VEuPathDB; FungiDB:ATCC64974_92700; -.
DR VEuPathDB; FungiDB:M747DRAFT_286938; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000236662; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..1793
FT /note="Non-reducing polyketide synthase adaA"
FT /id="PRO_0000446355"
FT DOMAIN 1716..1793
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:21866960"
FT REGION 16..250
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21866960"
FT REGION 391..824
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21866960"
FT REGION 923..1245
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21866960"
FT REGION 1312..1634
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21866960"
FT REGION 1642..1715
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1659..1712
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 561
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1753
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1793 AA; 194933 MW; 7F7CF92E7F857B73 CRC64;
MSAPTKLVFF GNEFPNDDLK ALFRGLHRHG KDRRFRQLAT FLEESTRVLQ NEVAQLPEPL
KKLVPHFENL MPLTEVDFRQ GPLGAAMESA LLTILELGMF IGHYEAEERV WDLSADRATL
AGLSIGLLAA AGVALSTHLA EVVQNGAECV RVSFRLGVYV HDISRKLEAP QADGSLLSWA
HVVTGETASD LQEELSRYNT ETGTPELLKV FISAADKTSV SVSGPPSRIR AAFRASQRLR
YSKSLALPVY DGLCHAAHLY DEETIHRVLH PDGSVIPTSR PVQLALLSSR SGQPFEATTA
AELFRAISTE LLTGTIFLDN ITAGILDRTE RCADATQCQI ETYRTSLVFK GLLKALEACF
PDRTISTTDL IPWVFQDYGA RQPKSCADSK LAIVGMACRM PGGANDLDLF WELLAQGRDT
HTTVPADRFD LETHYDPTGE TENATRTPFG NFIDQPGLFD AGFFNMSPRE AEQTDPMHRL
ALVTAYEALE MAGIVSGRTP SSNPKRIATF YGQASDDWRE LNASQNIGTY AVPGGERAFA
NGRINYFFKF GGPSFNLDTA CSSGLAAVQA ACSALWAGEA DTVLAGGLNI ITDPDNYAGL
GNGHFLSRTG QCKVWDQSAD GYCRADGVGS VVIKRLEDAE ADNDNILAVV LSAATNHSAE
AISITHPHAG AQKENYTQVL HQAAVNPLDI SYVELHGTGT QAGDAQEAES VLDIFAPRNH
RRRADQPLHL GAVKSNIGHG EAAAGIASLL KVLLMYQKNE IPAHIGIPTV INPAIPTDLE
QRKVYLPRTK TAWPRAAGQI RRAIVNSFGA HGGNTTLVLE DAPEKQVTVA REERSTHPVV
ISAKSKKSLA ANVETLLAYL DENPETDLGD LSYTTCARRM HHSWRLATAV SDIPALQKFL
RNAVSNDAVS QTRPIPTEAP PVVFTFTGQG AYYAGLAQGL FQALPFFRAE VRQLDHLSQR
LGFPSIVPVI LGEVEEGTAT ALVTQLSIVI VEIALARLWL LLLGIPAPHA VIGHSLGEYA
ALAVAGVLST ADALYLVGHR AQLIEEHCTP GSHAMLSVRA TIADIERLVG TGSDAPTYEL
SCQNTHQDTV IGGSIQDLNA IREKLEHEGI KCVNVDVPFA FHTAQMDAVR ERLAKAVAAV
PFKTPSVPVL SPLLGSVVFD GKSINPEYIV RATREPVQFA TAIDAAQELG IVNSQTLWVD
IGPHPICASF VRSLVPGARI VSSCRRNEDN FATMAKSLCT LHLAGRTPSW AEYFRPDEQA
YSLLRLPKYR WNEVNYWIQY LGTWTLDKAH LKNGGSQKRA ITDVPSISSL RTSLIHQVTE
ETVDKTTATL KAISDIQHPD FLEAVHGHTM NNCGVATSSI WTDMAMTVGE HLYRRLVPGT
DHVLMDLCDF EVQHAQVANT NSNTPQPLAL EAHLDLPTRH MSLAWYDVNA TTNQRADAPF
ATGSIKYPAD PTGAAWSIEW SRITHLIQGR IEALQHLAAE NKASTLSKPL AYALFKNVVD
YAPRYRGMDR VVIHDHEAFS DITLTTDRHG TWHTPPHWID SVSHLAGLVM NGSDASNTRD
FFYVTPGCSS CRMAEPLIAG GKYRNYVRMF PMPDEAHMYA GDLYILREDK IIGVVEQLKF
RRVPRLLMDR FFSPNKNAAA HAAPAPAPAA VPAVKKQPPT ETIQPQAPKT EQKQDQLQLP
NLASAAPSTA SSSSSPSSSG VATPTTEQEA PGADASAVTG VAGKCLELIA NETGLGVAEL
TADATFVQLG VDSLMSLVLS EKLRSEMGLE IKSSLFLECP TVGDLTGWLE QYC
